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Second most common lethal recessive disease in the
white population.
Neurological disorder (five types) that leads to severe amyotrophy with
respiratory insufficiency has been described. Clinical evolution according to the
type involved.
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Spinal Muscular Atrophy Type I (Werdnig-Hoffman Disease; SMA Infantile Acute
form; Infantile SMA)
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Spinal Muscular Atrophy Type II (Dubowitz Disease; Intermediate type of SMA;
Infantile Chronic form of SMA)
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Spinal Muscular Atrophy Type III (Juvenile Muscular Atrophy; Childhood-Onset
Proximal SMA; Kugelberg Welander Syndrome; Childhood Isolated SMA;
Wohlfart-Kugelberg-Welander Syndrome)
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Spinal Muscular Atrophy Type IV (Distal Hereditary Motor Neuropathy; Adult
Spinal Muscular Atrophy)
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Spinal Muscular Atrophy Type V or Adult Onset X-Linked SMA (Kennedy
Disease; Bulbospinal Muscular Atrophy)
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Autosomal recessive. However, some forms have
been suggested to be inherited as autosomal dominant and occasionally X-linked.
In adult onset (type IV), the causal gene is located on chromosome 12 (12q24).
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The disorder is characterized by degeneration and
loss of anterior horn cells in the spinal cord and sometimes also in the
brainstem, leading to symmetrical muscle weakness and wasting of voluntary
muscles. There is evidence that at least two identifiable genes are
associated with the disease: SMN1 (survival motor neurone) and NAIP (neuronal
apoptosis inhibitory protein), and possibly a third gene, BTF2p44 (basal
transcription factor 2H, subunit p44). The SMN gene is missing in the
majority of SMA patients and small, intragenic mutations have also been
associated with SMA. Approximately half of the severely affected patients
are also missing the NAIP gene, which may affect the severity of the
disease.
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Clinical features. CT scan and MRI are used to exclude other
pathologies. Electromyography usually shows neurogenic and occasional
myogenic pattern. Nerve conduction study is normal. Serum creatine kinase is
normal. Muscle biopsy shows a large number of round atrophic fibers and
clumps of hypertrophic fibers that are type I by ATPase reaction. DNA
testing for SMN and NAIP genes is reliable and confirmatory for the
phenotype. Prenatal DNA testing is less reliable because a small percentage
of population lack an SMN gene but are not clinically affected.
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Spinal Muscular Atrophy is the second most common
lethal autosomal recessive disease in the white population.
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Type I (Werdnig-Hoffman Disease): Early onset and diagnosis (before 3 months), with
severe intrauterine growth retardation, polyhydramnios, and tongue
fasciculations. Child never sits or walks. There is difficulty with
swallowing and feeding. Respiratory function is always severely impaired:
diaphragmatic breathing, respiratory infection, and distress. Absent deep
tendon reflexes, hypotonia, and weakness, but normal intelligence and no
sensory loss are observed. Restricted joint mobility and kyphoscoliosis are
also frequent. Death before age of 2 years old is common but does not always
occur.
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Type II (Dubowitz Disease or Chronic form): Intermediate SMA with onset between the
age of 3 and 18 months and survival beyond 4 years (usually ...